Fluorescein angiography compared to three-dimensional measurements by the retinal thickness analyzer in classic choroidal neovascularization

Purpose: To compare and correlate imaging of classic subfoveal choroidal neovascularization (CNV) with noninvasive 3-dimensional imaging by the retinal thickness analyzer (RTA) to conventional fluorescein angiography (FA). Methods: A total of 29 eyes of 29 consecutive patients with predominantly classic CNV eligible for photodynamic therapy underwent FA and RTA imaging. The FA dimensions of the CNV were measured independently by two graders. With the RTA, masked to FA the size of the CNV itself as imaged in 3-dimensional reconstruction, the size of significantly thickened retina overlying the CNV and the maximum retinal thickness were measured. Results: The mean diameter of the CNV determined from 3-dimensional RTA reconstructions showed an excellent correlation with measurements from FA (r = 0.91, p < 0.001). The area of retinal thickening was by a mean of 0.7 mm in diameter larger and correlated moderately well with the size of the CNV on FA (r = 0.65, p < 0.001). In contrast, there was no correlation between the absolute retinal thickness and the CNV size on FA. Conclusions: Noninvasive quantitative mapping of predominantly classic CNV by RTA is feasible and also allows 3-dimensional measurement of the lesion itself. The results correlate well with FA assessment but visualize different properties of the disease. Copyright (c) 2007 S. Karger AG, Basel

Global Saturation of Regularization Methods for Inverse Ill-Posed Problems

In this article the concept of saturation of an arbitrary regularization method is formalized based upon the original idea of saturation for spectral regularization methods introduced by A. Neubauer in 1994. Necessary and sufficient conditions for a regularization method to have global saturation are provided. It is shown that for a method to have global saturation the total error must be optimal in two senses, namely as optimal order of convergence over a certain set which at the same time, must be optimal (in a very precise sense) with respect to the error. Finally, two converse results are proved and the theory is applied to find sufficient conditions which ensure the existence of global saturation for spectral methods with classical qualification of finite positive order and for methods with maximal qualification. Finally, several examples of regularization methods possessing global saturation are shown.Comment: 29 page

Generalized Qualification and Qualification Levels for Spectral Regularization Methods

The concept of qualification for spectral regularization methods for inverse ill-posed problems is strongly associated to the optimal order of convergence of the regularization error. In this article, the definition of qualification is extended and three different levels are introduced: weak, strong and optimal. It is shown that the weak qualification extends the definition introduced by Mathe and Pereverzev in 2003, mainly in the sense that the functions associated to orders of convergence and source sets need not be the same. It is shown that certain methods possessing infinite classical qualification, e.g. truncated singular value decomposition (TSVD), Landweber's method and Showalter's method, also have generalized qualification leading to an optimal order of convergence of the regularization error. Sufficient conditions for a SRM to have weak qualification are provided and necessary and sufficient conditions for a given order of convergence to be strong or optimal qualification are found. Examples of all three qualification levels are provided and the relationships between them as well as with the classical concept of qualification and the qualification introduced by Mathe and Perevezev are shown. In particular, spectral regularization methods having extended qualification in each one of the three levels and having zero or infinite classical qualification are presented. Finally several implications of this theory in the context of orders of convergence, converse results and maximal source sets for inverse ill-posed problems, are shown.Comment: 20 pages, 1 figur

Ribose supplementation alone or with elevated creatine does not preserve high energy nucleotides or cardiac function in the failing mouse heart

Background: Reduced levels of creatine and total adenine nucleotides (sum of ATP, ADP and AMP) are hallmarks of chronic heart failure and restoring these pools is predicted to be beneficial by maintaining the diseased heart in a more favourable energy state. Ribose supplementation is thought to support both salvage and re-synthesis of adenine nucleotides by bypassing the rate-limiting step. We therefore tested whether ribose would be beneficial in chronic heart failure in control mice and in mice with elevated myocardial creatine due to overexpression of the creatine transporter (CrT-OE). Methods and Results: Four groups were studied: sham; myocardial infarction (MI); MI+ribose; MI+CrT-OE+ribose. In a pilot study, ribose given in drinking water was bioavailable, resulting in a two-fold increase in myocardial ribose-5-phosphate levels. However, 8 weeks post-surgery, total adenine nucleotide (TAN) pool was decreased to a similar amount (8–14%) in all infarcted groups irrespective of the treatment received. All infarcted groups also presented with a similar and substantial degree of left ventricular (LV) dysfunction (3-fold reduction in ejection fraction) and LV hypertrophy (32–47% increased mass). Ejection fraction closely correlated with infarct size independently of treatment (r2 = 0.63, p&lt;0.0001), but did not correlate with myocardial creatine or TAN levels. Conclusion: Elevating myocardial ribose and creatine levels failed to maintain TAN pool or improve post-infarction LV remodeling and function. This suggests that ribose is not rate-limiting for purine nucleotide biosynthesis in the chronically failing mouse heart and that alternative strategies to preserve TAN pool should be investigated

Myocardial creatine levels do not influence response to acute oxidative stress in isolated perfused heart

Background: Multiple studies suggest creatine mediates anti-oxidant activity in addition to its established role in cellular energy metabolism. The functional significance for the heart has yet to be established, but antioxidant activity could contribute to the cardioprotective effect of creatine in ischaemia/reperfusion injury. Objectives: To determine whether intracellular creatine levels influence responses to acute reactive oxygen species (ROS) exposure in the intact beating heart. We hypothesised that mice with elevated creatine due to over-expression of the creatine transporter (CrT-OE) would be relatively protected, while mice with creatine-deficiency (GAMT KO) would fare worse. Methods and Results: CrT-OE mice were pre-selected for creatine levels 20–100% above wild-type using in vivo 1 H– MRS. Hearts were perfused in isovolumic Langendorff mode and cardiac function monitored throughout. After 20 min equilibration, hearts were perfused with either H2O2 0.5 mM (30 min), or the anti-neoplastic drug doxorubicin 15 mM (100 min). Protein carbonylation, creatine kinase isoenzyme activities and phospho-PKCd expression were quantified in perfused hearts as markers of oxidative damage and apoptotic signalling. Wild-type hearts responded to ROS challenge with a profound decline in contractile function that was ameliorated by co-administration of catalase or dexrazoxane as positive controls. In contrast, the functional deterioration in CrT-OE and GAMT KO hearts was indistinguishable from wildtype controls, as was the extent of oxidative damage and apoptosis. Exogenous creatine supplementation also failed to protect hearts from doxorubicin-induced dysfunction. Conclusions: Intracellular creatine levels do not influence the response to acute ROS challenge in the intact beating heart, arguing against creatine exerting (patho-)physiologically relevant anti-oxidant activity